SYNTHESIS AND ALDOSE REDUCTASE INHIBITORY ACTIVITY OF N-(ARYLSULFONYL)GLYCINES AND N-(AROYL)-N-(ARYLMETHYLOXY)GLYCINES

Some N-(arylsulfonyl)- C and N-(aroyl)-N-(arylmethyloxy)glycines D wer e synthesised and tested as aldose reductase inhibitors (ARIs). They a re structurally related to the previously described ARIs of type A and B, from which they differ owing to the presence of a spacer, an OCH2 group, between the amino-acid nitrogen and the aromatic ring. The inhi bitory activity was evaluated on the bovine lens aldose reductase enzy me. Compounds of types C and D show an inhibitory activity which, in t he case of compounds D, is very similar to that reported for the paren t compounds B. Kinetic studies carried out on the most active compound (8a), reveal that it produces an inhibition which, depending on its c oncentration, may be either uncompetitive or noncompetitive with respe ct to the substrate and the cofactor.